Naslov
In silico analysis of potential structural and functional significance of human breast cancer gene BRCA2 sequence variants found in 5' untranslated region

Autori
Ozretić, Petar ; Levačić Cvok, Mirela ; Musani, Vesna ; Sabol, Maja ; Car, Diana ; Levanat, Sonja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
HDIR-1 „From Bench to Clinic“ : book of abstracts of the First meeting of the Croatian Association for Cancer Research with international participation / Sabol, Maja ; Levanat, Sonja - Zagreb : Hrvatsko društvo za istraživanje raka (HDIR), 2010, 30-30

Skup
HDIR-1 : First Meeting with International Participation : "From Bench to Clinic"

Mjesto i datum
Zagreb, Hrvatska, 11.11.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
breast cancer ; BRCA2 ; mRNA ; 5' UTR ; secondary structure

Sažetak
Untranslated regions (UTRs) are parts of the mature mRNA located before the start codon (5' UTR) and after the stop codon (3' UTR). They are transcribed with the coding region but they are not translated. Several regulatory roles have been assigned to the untranslated regions, including mRNA's localization and stability, and translational efficiency. These functions depend both on the sequence and structure of the UTRs. BRCA1 and BRCA2 are the major hereditary breast/ovarian cancer predisposing genes and their mutations increase the risk of developing cancer. Interpretation of sequence variants found in genetic testing is the major concern for BRCA genes, especially for risk assessment in genetic counseling. In general, for sequence variants found within the coding region of the genes it is much easier to predict their potential effects on the structure and function of the protein. Sequence variants that are found within untranslated and other regulatory genomic regions are much harder for interpretation. As it is known that the function of non-coding RNAs (ncRNAs) greatly depends on their secondary structure, we analyzed how sequence variants found in 5’ UTR of BRCA2 gene could have impact on predicted consensus secondary structure of this UTR. From UTRdb database we retrieved sequences of BRCA2 5’ UTR from four different species. We then used RNAalifold software to predict consensus secondary structure of BRCA2 5’ UTR to find out if there are substructures that have been conserved by evolution, as it is far more likely that conserved structures are functionally important. From different public databases (BIC, kConFab, SNPdb…) we collected BRCA2 5' UTR variants and using RNAfold tool we examined their potential functional significance that could be expressed by disrupting the consensus secondary substructures. By computational analysis of potential effects of BRCA2 5’ UTR sequence variants found in genetic testing of patients with breast/ovarian cancer we tried to find out if this in silico approach could be used for evaluation of sequence changes of unknown clinical significance in cancer etiology.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA